The Friend strain of the spleen focus-forming virus (SFFV), a replication-defective murine retrovirus, induces a rapid proliferation of erythroid precursor cells when it is injected as a pseudotype into susceptible mice. Two proteins encoded by SFFV have been identified, a gag gene-related protein and an env gene-related protein, gp52. In order to demonstrate which area(s) of the genome is responsible for the induction of disease, a genetic analysis of this virus has been initiated. The SFFV DNA has been molecularly cloned in a biologically active form. The gp52 protein is expressed in fibroblast cells after transfection and rescue of this cloned DNA. Furthermore, the level of gp52 expression correlates with the latency of disease induced in mice after injection of the virus produced by the transfected cells. Preliminary evidence using a molecularly cloned sub-genomic fragment of SFFV DNA indicates that the sequences necessary for the erythroproliferative disease and those encoding the gp52 are present in the same part of the viral genome; thus supporting the hypothesis that the gp52 is required for the disease.